Abstract

To explore the relationship of gut microbiota with the development of type 2 diabetes (T2DM), we analyzed 121 subjects who were divided into 3 groups based on their glucose intolerance status: normal glucose tolerance (NGT; n = 44), prediabetes (Pre-DM; n = 64), or newly diagnosed T2DM (n = 13). Gut microbiota characterizations were determined with 16S rDNA-based high-throughput sequencing. T2DM-related dysbiosis was observed, including the separation of microbial communities and a change of alpha diversity between the different glucose intolerance statuses. To assess the correlation between metabolic parameters and microbiota diversity, clinical characteristics were also measured and a significant association between metabolic parameters (FPG, CRP) and gut microbiota was found. In addition, a total of 28 operational taxonomic units (OTUs) were found to be related to T2DM status by the Kruskal-Wallis H test, most of which were enriched in the T2DM group. Butyrate-producing bacteria (e.g. Akkermansia muciniphila ATCCBAA-835, and Faecalibacterium prausnitzii L2-6) had a higher abundance in the NGT group than in the pre-DM group. At genus level, the abundance of Bacteroides in the T2DM group was only half that of the NGT and Pre-DM groups. Previously reported T2DM-related markers were also compared with the data in this study, and some inconsistencies were noted. We found that Verrucomicrobiae may be a potential marker of T2DM as it had a significantly lower abundance in both the pre-DM and T2DM groups. In conclusion, this research provides further evidence of the structural modulation of gut microbiota in the pathogenesis of diabetes.

Highlights

  • Type 2 diabetes mellitus (T2DM) has become one of the fastest growing public health problems in both developed and developing countries

  • body mass index (BMI), waist-hip ratio (WHR), fasting plasma glucose (FPG), 2HPG, fasting insulin (FINS), 2-hour insulin (2HINS), IR, and C-reactive protein (CRP) values were higher in the Pre-DM group than in the normal glucose tolerance (NGT) group (P,0.05)

  • The relative abundances of Verrucomicrobiae and Betaproteobacteria from NGT to Pre-DM and T2DM showed an opposite trend, while the relative abundance of Streptococcus continued to decrease from NGT to Pre-DM and to T2DM

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Summary

Introduction

Type 2 diabetes mellitus (T2DM) has become one of the fastest growing public health problems in both developed and developing countries. Prediabetes is even more prevalent than type 2 diabetes and there is an important demarcation line between the two conditions that indicates whether an individual is going to develop diabetes and cardiovascular disease [1,3]. The metagenomic sequencing of the human microbiome has revealed that there are 3.3 million non-redundant genes, with over 99% of the genes being of bacterial origin [6]. This gene set contains at least100-fold more genes than the complete human genome. With .50 species shared by 90% of the individuals studied, considerable variation occurs in both the types of microbes and in the diversity of microbial functional genes between individuals [6,7,8]

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